The thymus is an endocrine gland with functions unique to discrete periods of development. The establishment of its integrity prior to and during the perinatal period is crucial not only to the formation of a competent immune system but to the establishment of the hypothalamic-pituitary axis. It has further been suggested that these two functional aspects of the thymus may not be separate entities but rather part of an integrated network comprised of the nervous, endocrine and immune systems. In view of this possibility, we have undertaken anatomical, endocrine and immune studies to determine the nature and domain of this neuroendocrine-immune network. Utilizing horseradish peroxidase histochemistry we have mapped six discrete central nervous system projections directly to the thymus. Similarly, using light and ultrastructural analysis we have begun to determine the development and distribution of the cholinergic and catecholaminergic innervation of the thymus. Immunological and endocrinological studies also reveal abnormalities in the neurological mutant, stagger, that correlate with its aberrant thymic innervation pattern. In view of the aformentioned results, an extensive research program will be initiated to further evaluate the developemental and physiological function of the autonomic nervous system innervation of the thymus gland. Complete mapping of all the ANS contributions to the gland will be carried out utilizing neuroanatomical histochemistry and the light and ultrastructural microscopic level. An assessment of the function of thymic innervation will be carried out by examining the antigen specific cell mediated and humoral immune responses in both neuroimmune mutants and animal models. Human thymic material from various human neuroimmune diseases will be examined and compared to the pathological findings in their respective animal models.